The Northern Leopard frog, Rana pipiens, was the principal amphibian used in biomedical research and teaching. Researchers were, and still are, dependent on wild-caught frogs. Because of an unprecedented, decade-long decline in abundance of R. pipiens in the northern United States, researchers have become increasingly dependent upon other species of wild-caught leopard frogs imported from Mexico. Imported frogs are less desirable as a research resource in certain experiments becuase of their uncertain geographic origin, their imperfectly understood reproductive biology, and their inability to withstand storage in the laboratory. The objectives of the present study are to identify and to define the cause(s) of the reduction of frog populations in the northern United States. The geographic region chosen for study (from the Wisconsin border to the eastern Dakotas) includes pristine and disturbed conifer forests, hardwood forests, and grassland habitats. An additional site has been chosen in northwestern North Dakota because of the abundance of frogs there. Physico-chemical and biological characterization of frog habitats including lakes, sloughs, and wetlands will be related to population distribution, density, productivity, and mortality. Bacterial pathogens, a common renal tumor, the presence of heavy metal contaminants such as cadmium and lead, and residual carcass biocides will be studied seasonally with respect to habitat and population dynamics. Reproductive competence of frogs throughout the varied habitats will be measured. Adult blood cells will be cultured to detect chromosomal aberrations. It is our expectation that changes in one or more of these population characteristics over the next few years will provide the insight into causes of the current decline in leopard frogs that is necessary for the management and ultimate restoration of our indigenous Rana pipiens.